This invention relates to a system and method for manipulating small particles in a microfabricated fluid channel.
Microelectromechanical systems (MEMS) are very small, often moveable structures made on a substrate using surface or bulk lithographic processing techniques, such as those used to manufacture semiconductor devices. MEMS devices may be moveable actuators, sensors, valves, pistons, or switches, for example, with characteristic dimensions of a few microns to hundreds of microns. A moveable MEMS switch, for example, may be used to connect one or more input terminals to one or more output terminals, all microfabricated on a substrate. The actuation means for moveable MEMS devices may be thermal, piezoelectric, electrostatic, or magnetic, for example. MEMS devices may also be made which manipulate particles in a fluid stream passing by or through the MEMS device.
Such a particle manipulation device may be a MEMS movable valve, which can be used as a sorting mechanism for sorting various particles from a fluid stream, such as cells from blood. The particles may be transported to the sorting device within the fluid stream enclosed in a microchannel, which flows under pressure. Upon reaching the MEMS sorting device, the sorting device directs the particles of interest such as a blood stem cell, to a separate receptacle, and directs the remainder of the fluid stream to a waste receptacle.
MEMS-based cell sorter systems have been proposed as an improvement to existing fluorescence-activated cell sorting systems (FACS) known as flow cytometers. Flow cytometers are generally large and expensive systems which sort cells based on a fluorescence signal from a tag affixed to the cell of interest. The cells are diluted and suspended in a sheath fluid, and then separated into individual droplets via rapid decompression through a nozzle. After ejection from the nozzle, the droplets are separated into different bins electrostatically, based on the fluorescence signal from the tag. Among the issues with these systems are cell damage or loss of functionality due to the decompression, difficult and costly sterilization procedures between samples, inability to sort sub-populations along different parameters, and substantial training necessary to own, operate and maintain these large, expensive pieces of equipment. For at least these reasons, use of flow cytometers has been restricted to large hospitals and laboratories and the technology has not been accessible to smaller entities.
A MEMS-based cell sorter may have substantial advantages at least in terms of size, cost and complexity over existing FACS flow cytometers. A number of patents have been granted which are directed to such MEMS-based cell sorting devices. For example, U.S. Pat. No. 6,838,056 (the '056 patent) is directed to a MEMS-based cell sorting device, U.S. Pat. No. 7,264,972 (the '972 patent) is directed to a micromechanical actuator for a MEMS-based cell sorting device. U.S. Pat. No. 7,220,594 (the '594 patent) is directed to optical structures fabricated with a MEMS cell sorting apparatus, and U.S. Pat. No. 7,229,838 (the '838 patent) is directed to an actuation mechanism for operating a MEMS-based particle sorting system. Each of these patents is hereby incorporated by reference.
Such particle sorting devices may be examples of a broader category of particle manipulation systems, which may perform some manipulation on the particles passing by in a fluid stream. The stream may include target particles as well as non-target materials. The manipulation may be to apply a charge, apply a force, apply a field, or apply laser light, to the target particles, for example. The purpose may by to identify, alter or destroy the target particles. Alternatively, the purpose may be to distinguish target particles from non-target materials, and/or to separate them from the remainder of the fluid stream.